Ghana international Thomas-Asante converted his seventh and eighth goals of the season, before Makenzie Kirk's delightful lob in added time, to move the unbeaten Sky Blues four points clear at the summit.
Australians Adrian Segecic (64th minute) and Hayden Matthews (80th) were both brought on in the second half after Portsmouth had gone 2-0 down, but Coventry held on to please 2186 travelling fans and end Pompey's three-game unbeaten run.
Portsmouth's loss was compounded by an injury to Segecic.
The 21-year-old, who had only been on the field for about 10 minutes, injured his left ankle and was reportedly in tears after being forced off the ground.
Segecic, who was part of the Socceroos squad for last month's series against New Zealand, had been hoping to earn his first cap for Australia.
Portsmouth had prided themselves on being a graveyard for top-spot teams, having knocked Middlesbrough and Preston North End off the summit already this season - but could not down the Sky Blues.
The home side felt they should have taken the lead in the 15th minute when Jay Dasilva appeared to block Yang Min-hyeok's cross with his arm.
The protests were waved away by referee Gavin Ward, before fourth official Stephen Martin had to get in the middle of managers Lampard and John Mousinho after some unfriendly words and chest prods.
"It looks a clear penalty to me. The ball strikes his arm way outside of the body," the Pompey head coach said.
"But there is no needle with Lampard. I just spoke to him there and my main problem is with the officiating team for not dealing with it differently.
"It is a disappointing result, but I think it was a fair result overall. We got ourselves back into the game too little, too late."
Elsewhere on Tuesday night, third-placed Millwall, Bristol City (fourth) and Charlton Athletic (fifth) all enjoyed victories.
Hull City, Derby County and Birmingham City also recorded wins in round 11.
Sheffield United scored a 3-1 success at Blackburn to move out of the relegation zone and leave Socceroos defender Lewis Miller's Rovers 23rd in the 24-team league.
Another four matches take place on Wednesday, including second-placed Boro at bottom-of-the-table Sheffield Wednesday.
With AAP.
